(R)-α-methyl-N-[3-[3-(trifluoromethyl)phenyl]propyl]-1-naphthalenemethane amine (herein “Cinacalcet” or “CNC”) has a CAS number of 226256-56-0, a formula of C22H22F3N and the following structure:

Cinacalcet is the free base form of Cinacalcet hydrochloride (herein “CNC-HCl”), which has a CAS number of 364782-34-3 and the following structure:

CNC-HCl is marketed as SENSIPAR™, and was the first drug in a class of compounds known as calcimimetics to be approved by the FDA. Calcimimetics are a class of orally active, small molecules that decrease the secretion of parathyroid hormone (“PTH”) by activating calcium receptors. The secretion of PTH is normally regulated by the calcium-sensing receptor. Calcimimetics increase the sensitivity of this receptor to calcium, which inhibits the release of parathyroid hormone, and lowers parathyroid hormone levels within a few hours. Calcimimetics are used to treat hyperparathyroidism, a condition characterized by the over-secretion of PTH that results when calcium receptors on parathyroid glands fail to respond properly to calcium in the bloodstream. Elevated levels of PTH, an indicator of secondary hyperparathyroidism, are associated with altered metabolism of calcium and phosphorus, which can result in bone pain, fractures, and an increased risk for cardiovascular death. As a calcimimetic, CNC-HCl is approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease, who are on dialysis. Treatment with CNC-HCl lowers serum levels of PTH as well as the calcium/phosphorus ion product, a measure of the amount of calcium and phosphorus in the blood.
Inorganic ion receptor-active molecules, especially calcium receptor-active molecules, such as those having the general structure of Cinacalcet, are disclosed in U.S. Pat. No. 6,011,068. U.S. Pat. No. 6,211,244 discloses calcium receptor-active compounds related to Cinacalcet and methods of making such compounds. Cinacalcet and its enantiomer may be produced by various methods, using the processes disclosed in U.S. Pat. No. 6,211,244; DRUGS OF THE FUTURE, 27 (9), 831 (2002); U.S. Pat. Nos. 5,648,541, 4,966,988; and Tetrahedron Letters (2004) 45: 8355, footnote 12.
The present invention relates to the solid state physical properties of Cinacalcet hydrochloride. These properties can be influenced by controlling the conditions under which Cinacalcet hydrochloride is obtained in solid form. Solid state physical properties include, for example, the flowability of the milled solid, the rate of dissolution in an aqueous fluid, behavior on compaction, and storage stability. The discovery of new processes of preparing such polymorphic forms provides opportunities to improve the performance characteristics of a pharmaceutical product.
The FDA's published Summary Basis of Approval of New Drug Application #21688 mentions that Cinacalcet hydrochloride has only one stable crystalline form at ambient temperature. However, there is no prior art disclosure of a process for preparing crystalline cinacalcet hydrochloride. Therefore, there is a need in the art for additional processes for the preparation of crystalline cinacalcet hydrochloride.